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In the present study, we investigated the role of the serine\/threonine kinase Akt in angiogenesis. Silencing of Akt1 in human umbilical vein endothelial cells significantly inhibited vascular endothelial growth factor (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>)\u2010induced capillary\u2010like tube formation. Mice lacking Akt1 exhibited impaired retinal angiogenesis with delayed endothelial cell (<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>) proliferation. In addition, <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010induced corneal angiogenesis and tumor development were significantly inhibited in mice lacking Akt1. Loss of Akt1 resulted in reduced angiogenic sprouting, as well as the proliferation of <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>s and mural cells. Addition of culture supernatant of vascular smooth muscle cells (<jats:styled-content style=\"fixed-case\">VSMC<\/jats:styled-content>s) in which Akt1 was silenced suppressed tube formation, the stability of preformed tubes and the proliferation of <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>s. In addition, attachment of <jats:styled-content style=\"fixed-case\">VSMC<\/jats:styled-content>s to <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>s was significantly reduced in cells in which Akt1 was silenced. Mural cell coverage of retinal vasculature was reduced in mice lacking Akt1. Finally, mice lacking Akt1 showed severe retinal hemorrhage compared to the wild\u2010type. These results suggest that the regulation of <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content> function and mural cell coverage by Akt1 is important for blood vessel maturation during angiogenesis.<\/jats:p>","DOI":"10.1002\/2211-5463.12621","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T04:51:54Z","timestamp":1551847914000},"page":"801-813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage"],"prefix":"10.1002","volume":"9","author":[{"given":"Jung Min","family":"Ha","sequence":"first","affiliation":[{"name":"Biomedical Research Institute Gene and Cell Therapy Center for Vessel Associated Disease Department of Pharmacology Pusan National University School of Medicine Yangsan Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo 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